SARS-CoV-2 evolution during treatment of chronic infection.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Genomic and geographical structure of human cytomegalovirus.

Human cytomegalovirus (CMV) has infected humans since the origin of our species and currently infects most of the world's population. Variability between CMV genomes is the highest of any human herpesvirus, yet large portions of the genome are conserved. Here, we show that the genome encodes 74 regions of relatively high variability each with 2 to 8 alleles. We then identified two patterns in the CMV genome. Conserved parts of the genome and a minority (32) of variable regions show geographic population structure with evidence for African or European clustering, although hybrid strains are present. We find no evidence that geographic segregation has been driven by host immune pressure affecting known antigenic sites. Forty-two variable regions show no geographical structure, with similar allele distributions across different continental populations. These "nongeographical" regions are significantly enriched for genes encoding immunomodulatory functions suggesting a core functional importance. We hypothesize that at least two CMV founder populations account for the geographical differences that are largely seen in the conserved portions of the genome, although the timing of separation and direction of spread between the two are not clear. In contrast, the similar allele frequencies among 42 variable regions of the genome, irrespective of geographical origin, are indicative of a second evolutionary process, namely balancing selection that may preserve properties critical to CMV biological function. Given that genetic differences between CMVs are postulated to alter immunogenicity and potentially function, understanding these two evolutionary processes could contribute important information for the development of globally effective vaccines and the identification of novel drug targets.

Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients.

Chronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution.

Quantifying EHR and Policy Factors Associated with the Gender Productivity Gap in Ambulatory, General Internal Medicine.

BACKGROUND: The gender gap in physician compensation has persisted for decades. Little is known about how differences in use of the electronic health record (EHR) may contribute. OBJECTIVE: To characterize how time on clinical activities, time on the EHR, and clinical productivity vary by physician gender and to identify factors associated with physician productivity. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included general internal medicine physicians employed by a large ambulatory practice network in the Northeastern United States from August 2018 to June 2021. MAIN MEASURES: Monthly data on physician work relative value units (wRVUs), physician and practice characteristics, metrics of EHR use and note content, and temporal trend variables. KEY RESULTS: The analysis included 3227 physician-months of data for 108 physicians (44% women). Compared with men physicians, women physicians generated 23.8% fewer wRVUs per month, completed 22.1% fewer visits per month, spent 4.0 more minutes/visit and 8.72 more minutes on the EHR per hour worked (all p < 0.001), and typed or dictated 36.4% more note characters per note (p = 0.006). With multivariable adjustment for physician age, practice characteristics, EHR use, and temporal trends, physician gender was no longer associated with productivity (men 4.20 vs. women 3.88 wRVUs/hour, p = 0.31). Typing/dictating fewer characters per note, relying on greater teamwork to manage orders, and spending less time on documentation were associated with higher wRVUs/hour. The 2021 E/M code change was associated with higher wRVUs/hour for all physicians: 10% higher for men physicians and 18% higher for women physicians (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: Increased team support, briefer documentation, and the 2021 E/M code change were associated with higher physician productivity. The E/M code change may have preferentially benefited women physicians by incentivizing time-intensive activities such as medical decision-making, preventive care discussion, and patient counseling that women physicians have historically spent more time performing.

Selection for cooperativity causes epistasis predominately between native contacts and enables epistasis-based structure reconstruction.

Epistasis and cooperativity of folding both result from networks of energetic interactions in proteins. Epistasis results from energetic interactions among mutants, whereas cooperativity results from energetic interactions during folding that reduce the presence of intermediate states. The two concepts seem intuitively related, but it is unknown how they are related, particularly in terms of selection. To investigate their relationship, we simulated protein evolution under selection for cooperativity and separately under selection for epistasis. Strong selection for cooperativity created strong epistasis between contacts in the native structure but weakened epistasis between nonnative contacts. In contrast, selection for epistasis increased epistasis in both native and nonnative contacts and reduced cooperativity. Because epistasis can be used to predict protein structure only if it preferentially occurs in native contacts, this result indicates that selection for cooperativity may be key for predicting structure using epistasis. To evaluate this inference, we simulated the evolution of guanine nucleotide-binding protein (GB1) with and without cooperativity. With cooperativity, strong epistatic interactions clearly map out the native GB1 structure, while allowing the presence of intermediate states (low cooperativity) obscured the structure. This indicates that using epistasis measurements to reconstruct protein structure may be inappropriate for proteins with stable intermediates.

Comparison of DXA-based versus CT-based indices to predict prevalent fracture history in men with spinal cord injury.

Fracture risk prediction remains challenging in adults with spinal cord injury. Here, we compare the ability of CT- and DXA-derived indices to discriminate between those with and without prevalent osteoporotic fracture. Novel CT-derived indices may offer improved assessment of fragility fracture risk as well as improved monitoring of response to therapies. INTRODUCTION: Individuals with spinal cord injury are particularly susceptible to osteoporosis. As advanced imaging techniques become more readily available clinically, there is limited information on the relative strength of various outcomes for fracture risk prediction. The purpose of this study was to compare the ability of DXA-based versus CT-based indices to predict prevalent fracture history in adults with spinal cord injury. METHODS: Thirty-six men with known SCI underwent dual energy X-ray absorptiometry and computed tomography assessments of the lower extremities. We used age-adjusted area under the curve models to compare the predictive value for each bone parameter to identify prevalent fracture history. RESULTS: CT-based indices outperformed DXA-based indices at all sites. The site with the highest AUC was the trabecular BMD at the proximal tibial epiphysis. CONCLUSIONS: CT imaging may have clinical utility to improve fracture risk prediction in adults with SCI. More work is needed to confirm these findings and to assess the value of CT-based indices to predict incident fracture, monitor longitudinal bone loss, and monitor response to various therapies, both pharmacological and rehabilitation.

Longitudinal Trends in Severe Traumatic Brain Injury Inpatient Rehabilitation.

OBJECTIVE: The goal of this study is to describe national trends in inpatient rehabilitation facility (IRF) discharges for the most severely disabled cohort of patients with traumatic brain injury (TBI). METHODS: Data from the Uniform Data System for Medical Rehabilitation for patients discharged from an IRF between January 1, 2002, and December 31, 2017, with a diagnosis of TBI and an admission Functional Independence Measure of 18, the lowest possible score, were obtained and analyzed. RESULTS: Of the 252 112 patients with TBI discharged during the study period, 10 098 met the study criteria. From 2002 to 2017, the number of patients with an IRF admission Functional Independence Measure of 18 following TBI discharged from IRFs annually decreased from 649 to 488, modeled by a negative regression (coefficient = -2.97; P = .001), and the mean age (SD) increased from 43.0 (21.0) to 53.7 (21.3) years (coefficient = 0.70; P < .001). During the study period, the number of patients with the most severe disability on admission to IRF who were discharged annually as a proportion of total patients with TBI decreased from 5.5% to 2.5% (odds ratio = 0.95; P < .001) and their mean length of stay decreased from 41.5 (36.2) to 29.3 (24.9) days (coefficient = -0.83; P < .001]. CONCLUSION: The number and proportion of patients with the most severe disability on IRF admission following TBI who are discharged from IRFs is decreasing over time. This may represent a combination of primary prevention, early mortality due to withdrawal of life-sustaining treatment, alternative discharge dispositions, or changes in admitting and reimbursement practices. Furthermore, there has been a decrease in the duration of IRF level care for these individuals, which could ultimately lead to poorer functional outcomes, particularly given the importance of specialized rehabilitative care in this population.

Sudden Unexplained Death in Childhood: Current Understanding.

ABSTRACT: Sudden unexplained death in childhood is a term that encompasses apparently natural deaths in children aged older than 1 year with no discernible cause despite a thorough assessment. Definitive underlying causes vary but most cases remain largely unexplained. Research has furthered the view that sudden unexplained death in childhood is not an accident, but rather a sentinel medical event for which a thorough postmortem investigation is indicated. Emerging evidence in genetics, neurology, and neuropathology point to heterogeneous causes that in some cases share features of recognized diseases.

Genetic Determinants of Sudden Unexpected Death in Pediatrics.

PURPOSE: This study aimed to evaluate genetic contributions to sudden unexpected death in pediatrics (SUDP). METHODS: We phenotyped and performed exome sequencing for 352 SUDP cases. We analyzed variants in 294 "SUDP genes" with mechanisms plausibly related to sudden death. In a subset of 73 cases with parental data (trios), we performed exome-wide analyses and conducted cohort-wide burden analyses. RESULTS: In total, we identified likely contributory variants in 37 of 352 probands (11%). Analysis of SUDP genes identified pathogenic/likely pathogenic variants in 12 of 352 cases (SCN1A, DEPDC5 [2], GABRG2, SCN5A [2], TTN [2], MYBPC3, PLN, TNNI3, and PDHA1) and variants of unknown significance-favor-pathogenic in 17 of 352 cases. Exome-wide analyses of the 73 cases with family data additionally identified 4 de novo pathogenic/likely pathogenic variants (SCN1A [2], ANKRD1, and BRPF1) and 4 de novo variants of unknown significance-favor-pathogenic. Comparing cases with controls, we demonstrated an excess burden of rare damaging SUDP gene variants (odds ratio, 2.94; 95% confidence interval, 2.37-4.21) and of exome-wide de novo variants in the subset of 73 with trio data (odds ratio, 3.13; 95% confidence interval, 1.91-5.16). CONCLUSION: We provide strong evidence for a role of genetic factors in SUDP, involving both candidate genes and novel genes for SUDP and expanding phenotypes of disease genes not previously associated with sudden death.

Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients.

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.

Trauma Indicators in Spinal Cord Injury Rehabilitation Outcomes: A Retrospective Cohort Analysis of the National Trauma Data Bank and National Spinal Cord Injury Database.

OBJECTIVE: To investigate whether initial emergency department physiological measures and metrics of trauma severity predict functional outcomes and neurologic recovery in traumatic spinal cord injury. DESIGN: Retrospective analysis of a clinical database. SETTING: Merged multicenter data from the Spinal Cord Injury Model Systems (SCIMS) database and National Trauma Data Bank from 6 academic medical centers across the United States. PARTICIPANTS: Patients (N=319) admitted to SCIMS rehabilitation centers within 1 year of injury. The majority of patients were men (76.2%), with a mean age of 44 years (SD, 19y). At rehabilitation admission, the most common neurologic level of injury was low cervical (C5-C8, 39.5%) and ASIA impairment scale (AIS) was A (34.4%). MAIN OUTCOME MEASURES: Primary outcomes were FIM motor score at discharge from inpatient rehabilitation and change in FIM motor score between inpatient rehabilitation admission and discharge. We hypothesized that derangements in emergency department physiological measures, such as decreased blood pressure and oxygen saturation, as well as increased severity of trauma burden, would predict poorer functional outcomes. RESULTS: Linear regression analysis showed that neurologic level of injury and AIS predicted discharge FIM motor score. Systolic blood pressure, heart rate, oxygen saturation, need for assisted respiration, and presence of penetrating injury did not predict discharge motor FIM or FIM motor score improvement. CONCLUSIONS: Initial emergency department physiological parameters did not prognosticate functional outcomes in this cohort.

For-Profit and Not-for-Profit Inpatient Rehabilitation in Traumatic Brain Injury: Analysis of Demographics and Outcomes.

OBJECTIVE: To describe differences in characteristics and outcomes of patients with traumatic brain injury by inpatient rehabilitation facility (IRF) profit status. DESIGN: Retrospective database review using the Uniform Data System for Medical Rehabilitation. SETTING: IRFs. PARTICIPANTS: Individual discharges (N=53,630) from 877 distinct rehabilitation facilities for calendar years 2016 through 2018. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Patient demographic data (age, race, primary payer source), admission and discharge FIM, FIM gain, length of stay efficiency, acute hospital readmission from for-profit and not-for-profit IRFs within 30 days, and community discharges by facility profit status. RESULTS: Patients at for-profit facilities were significantly older (69.69 vs 64.12 years), with lower admission FIM scores (52 vs 57), shorter lengths of stay (13 vs 15 days), and higher discharge FIM scores (88 vs 86); for-profit facilities had higher rates of community discharges (76.8% vs 74.6%) but also had higher rates of readmission (10.3% vs 9.9%). CONCLUSIONS: The finding that for-profit facilities admit older patients who are reportedly less functional on admission and more functional on discharge, with higher rates of community discharge but higher readmission rates than not-for-profit facilities is an unexpected and potentially anomalous finding. In general, older, less functional patients who stay for shorter periods of time would not necessarily be expected to make greater functional gains. These differences should be further studied to determine if differences in patient selection, coding and/or billing, or other unreported factors underlie these differences.

Association between weekly exercise minutes and resting IL-6 in adults with chronic spinal cord injury: findings from the fracture risk after spinal cord injury exercise study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess associations between weekly aerobic exercise minutes and resting interleukin-6 (IL-6), C-reactive protein (CRP), or leptin levels in adults with chronic spinal cord injury (SCI). SETTING: Three hundred and forty-four community-dwelling men and women with SCI duration of > 1 year. METHODS: CRP, IL-6, and leptin levels were quantified by ultra-sensitive enzyme-linked immunoassay. Smoking, medication use, comorbidities, and aerobic exercise minutes per week were assessed by self-reported questionnaire. Body composition was determined by whole-body dual-energy X-ray absorptiometry. Generalized linear models were used to assess associations. RESULTS: In multivariable modeling, resting IL-6 levels were 0.001 pg/mL lower for every 1 min of weekly aerobic exercise. IL-6 levels increased with increasing android-to-gynoid fat ratio, in active/ever smokers compared to never smokers, and in individuals with skin pressure injuries compared to those without. IL-6 levels were lower in active ibuprofen users compared to nonusers. We found no association between weekly exercise minutes and CRP or leptin when designing similar models. CONCLUSIONS: Increasing aerobic exercise minutes is associated with lower IL-6 levels in adults with chronic SCI when considering body composition, smoking, skin pressure injuries, and ibuprofen use. CRP and leptin did not demonstrate an association with exercise when considering the similar variables. The use of these biomarkers in assessing the therapeutic value of future exercise-related interventions will be paramount for meaningful health improvement among those with SCI. Although a large, prospective dataset, this cross-sectional study cannot assign causation. Future prospective studies are needed to confirm these findings.

Positive selection in dNTPase SAMHD1 throughout mammalian evolution.

The vertebrate protein SAMHD1 is highly unusual in having roles in cellular metabolic regulation, antiviral restriction, and regulation of innate immunity. Its deoxynucleoside triphosphohydrolase activity regulates cellular dNTP concentration, reducing levels below those required by lentiviruses and other viruses to replicate. To counter this threat, some primate lentiviruses encode accessory proteins that bind SAMHD1 and induce its degradation; in turn, positive diversifying selection has been observed in regions bound by these lentiviral proteins, suggesting that primate SAMHD1 has coevolved to evade these countermeasures. Moreover, deleterious polymorphisms in human SAMHD1 are associated with autoimmune disease linked to uncontrolled DNA synthesis of endogenous retroelements. Little is known about how evolutionary pressures affect these different SAMHD1 functions. Here, we examine the deeper history of these interactions by testing whether evolutionary signatures in SAMHD1 extend to other mammalian groups and exploring the molecular basis of this coevolution. Using codon-based likelihood models, we find positive selection in SAMHD1 within each mammal lineage for which sequence data are available. We observe positive selection at sites clustered around T592, a residue that is phosphorylated to regulate SAMHD1 activity. We verify experimentally that mutations within this cluster affect catalytic rate and lentiviral restriction, suggesting that virus-host coevolution has required adaptations of enzymatic function. Thus, persistent positive selection may have involved the adaptation of SAMHD1 regulation to balance antiviral, metabolic, and innate immunity functions.

Human cytomegalovirus haplotype reconstruction reveals high diversity due to superinfection and evidence of within-host recombination.

Recent sequencing efforts have led to estimates of human cytomegalovirus (HCMV) genome-wide intrahost diversity that rival those of persistent RNA viruses [Renzette N, Bhattacharjee B, Jensen JD, Gibson L, Kowalik TF (2011) PLoS Pathog 7:e1001344]. Here, we deep sequence HCMV genomes recovered from single and longitudinally collected blood samples from immunocompromised children to show that the observations of high within-host HCMV nucleotide diversity are explained by the frequent occurrence of mixed infections caused by genetically distant strains. To confirm this finding, we reconstructed within-host viral haplotypes from short-read sequence data. We verify that within-host HCMV nucleotide diversity in unmixed infections is no greater than that of other DNA viruses analyzed by the same sequencing and bioinformatic methods and considerably less than that of human immunodeficiency and hepatitis C viruses. By resolving individual viral haplotypes within patients, we reconstruct the timing, likely origins, and natural history of superinfecting strains. We uncover evidence for within-host recombination between genetically distinct HCMV strains, observing the loss of the parental virus containing the nonrecombinant fragment. The data suggest selection for strains containing the recombinant fragment, generating testable hypotheses about HCMV evolution and pathogenesis. These results highlight that high HCMV diversity present in some samples is caused by coinfection with multiple distinct strains and provide reassurance that within the host diversity for single-strain HCMV infections is no greater than for other herpesviruses.

The parental role before and after SIDS.

Role confusion is a prominent constituent symptom of Prolonged Grief Disorder in parents after their infants die from sudden infant death syndrome (SIDS). We interviewed 31 parents of SIDS infants 2-5 years post-loss examining the parental role before death, at the time of loss, and in bereavement. Thematic analysis found disruption of the role and re-imagined responsibilities for their child's physical security, emotional security, and meaning. Tasks within these domains changed from concrete and apparent to representational and self-generated. Parents in bereavement locate ongoing, imperative parental responsibilities, particularly asserting their child's meaningful place in the world and in their family.

Viral CpG Deficiency Provides No Evidence That Dogs Were Intermediate Hosts for SARS-CoV-2.

Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.

Predicted norovirus resurgence in 2021-2022 due to the relaxation of nonpharmaceutical interventions associated with COVID-19 restrictions in England: a mathematical modeling study.

BACKGROUND: To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. METHODS: Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. RESULTS: We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. CONCLUSIONS: Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Resilience and mental health in individuals with spinal cord injury during the COVID-19 pandemic.

STUDY DESIGN: Cross-sectional, observational study. OBJECTIVES: To understand how resilience, access to personal care attendants (PCAs) and medical supplies, and concerns about medical rationing, finances, and social isolation are related to overall and mental health in individuals with spinal cord injury (SCI) in the context of the COVID-19 pandemic. SETTING: Community dwelling adults (N = 187) with SCI. METHODS: Data were collected online between May 1, 2020 and August 31, 2020. Outcomes were overall and mental health, depression and anxiety symptoms, and quality of life (QoL). Predictors were resilience, access to PCAs and medical supplies, and concerns about medical rationing, finances, and social isolation. RESULTS: Incomplete injury, concern about medical rationing, medical supply disruption, and social isolation predicted a greater perceived impact of the pandemic on overall heath. Younger age, decreased resilience, and concern about medical rationing and social isolation predicted greater perceived impact of the pandemic on mental health. Decreased resilience and concern about medical rationing and finances predicted increased anxiety symptoms. Incomplete injury, believing that medical rationing was occurring, decreased resilience, and concern about finances and social isolation predicted increased depressive symptoms. Decreased resilience and concern about finances, medical rationing, and social isolation predicted lower QoL. CONCLUSIONS: The negative effects of the pandemic on the overall and mental health of individuals with SCI may be ameliorated by resilience. In future crises, it may be beneficial to screen individuals for resilience so that those with decreased resilience are offered the appropriate resources to enhance resilience and improve overall wellbeing.